role of kidneys in the regulation of acid-base balance

7/30/2019 Role of Kidneys in the Regulation of Acid-Base Balance

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Role of The Kidneys in The

Regulation of Acid-Base BalanceRichard Thomas P. Lim, MD

Assistant Professor I

Department of PhysiologyJonelta Foundation School of Medicine

January 22, 2013


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Outline

I. The Bicarbonate Buffer System

II. Overview of Acid-Base Balance

III. Net Acid Excretion by The KidneysA. Bicarbonate Reabsorption Along the Nephron

B. Regulation of H Secretion

C. Formation of New Bicarbonate


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IV. Response to Acid-Base DisordersA. Extracellular and Intracellular Buffers

B. Respiratory Compensation

C. Renal Compensation

V. Simple Acid-Base DisordersA. Types of Acid-Base Disorders

1. Metabolic Acidosis

2. Metabolic Alkalosis

3. Respiratory Acidosis4. Respiratory Alkalosis

B. Analysis of Acid-Base Disorders


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Acids and Bases

Diet

Cellular metabolism

Kidney, lungs, liver

Acid adds H to body fluids

Alkali removes H from body fluids

Each day, we ingest a variety of acidic and basic substances. Also, cellular metabolismproduces acids and bases. Without proper regulation of the pH of the body, many

biochemical reactions necessary for life might not occur. For this lecture, we will be

focusing on how the kidneys regulate the bodys pH. However, aside from the kidneys,

the lungs and liver also help in maintaining a normal pH of the body. An acid is defined

as any substance that adds H to body fluids while alkali or bases remove H from the body

fluids.


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Bicarbonate Buffer System

Buffer of ECF

Regulated by both kidneys and the lungsCarbonic anhydrase

Rate-limiting step

The bicarbonate buffer system is an important buffer of ECF. It can potentially buffer up

to 350meq of H. It is different from the other buffer systems in the body, such as the

phosphate, because it is regulated by both the kidneys and the lungs.

The first reaction is slow, and is the rate-limiting step. The enzyme carbonic anhydrase

speeds up this reaction. The dissociation of carbonic acid occurs instantaneously.


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Change in bicarbonate metabolic acid-base disorder

Change in PCO2 respiratory acid-base disorder

Kidneys bicarbonate

Lungs PCO2This equation is derived from the HH equation. Suffice it to say at this point that any

change in PCO2 or any change in bicarbonate will alter the pH or the H concentration of

the body. When the alteration in pH is due to a change in bicarbonate, this is called a

metabolic acid-base disorder. When the alteration in pH is due to a change in PCO2, this

is called a respiratory acid-base disorder. The kidneys are responsible for regulating the

bicarbonate while the lungs regulate the PCO2


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Acid Balance

Acid production/ingestion = acid excretion

Acidosis addition > excretion

Alkalosis addition < excretion

As we have discussed repeatedly in the past, regulation of any compound in the

body depends on the amount ingested or produced and the amount excreted.

Ingestion of acidic comounds, or the production of acids from cellular

metabolism must be equal to the amount of acid excreted in order to maintain a

normal body pH. If addition of H is greater than the excretion, acidosis results. If

excretion is more than the addition of H, aklasis will occur.


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Volatile and Non-volatile

Volatile acid derived from CO2; eliminated

immediately; does not impact acid-base

balance

Non-volatile acid not derived from CO2s

Carbon dioxide is eliminated immediately from the lungs. Because of this, CO2

does not impact acid-base balance. It is the only volatile acid. It is called as suchbecause it has the potential to generate H from the hydration of CO2. All the

other acids produced in the body are non-volatile acids. These are acids not

derived from CO2.


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Dietary intake meat

Cellular metabolism

Feces bicarbonate loss

Net addition of nonvolatile acid


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Normally, the body gets a net addition of nonvolatile acids from

different processes. These nonvolatile acids are immediately neutralized

by bicarbonate.

Intake of meat, composed of protein amino acids yield a net

production of acids. Metabolism of certain amino acids yield acids,

while only a few result to production of a basic compound. Thus dietary

intake of meat yield acids. Cellular metabolism also result to a net

production of acids. Bicarbonate is also lost in the feces. All of theseprocesses result in a net addition of volatile acids. Remember that

volatile acids are acids not derived from the hydration of carbon

dioxide.

The acids formed from these processes are neutralized by bicarbonate,

thereby forming Na salts and consuming bicarbonate in the process. Tocontinually neutralize these acids, the kidneys must be able to replenish

the bicarbonate needed. Our bicarbonate stores, if not replenished

would only last us 5 days.


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Net Acid Excretion by Kidneys

Acid excretion = acid production

Prevent bicarbonate loss in urine 4320 meq HCO3 filtered load

100meq HCO3 needed for nonvolatile acids

Normally, the acid excreted by the kidneys is equual to the amount of acidproduction. In addition, the kidneys must also prevent loss of bicarbonate in the

urine, because we need the bicarbonate to neutralize the production of nonvolatile

acids. The filtered load of bicarbonate is about 4320 meq/day, while only 100meq of

HCO3 are needed to neutralize the production of nonvolatile acids. The reabsorption

of HCO3 is quantitately more important because we can potentially lose so much

HCO3 from the urine.


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Titratable Acids

Way of excreting H Urinary buffers phosphate, creatinine

Maximum urine pH 4.0

Way of excreting excess H beyond maximum

pH

The kidneys are unable to excrete urine with a pH of less than 4.0. Therefore, if the

urine has a pH of 4.0 already, how will the kidneys excrete the excess H? Another way

of excreting H, aside from being secreted as H in the urine is via titratable acids.

These collective term refer to compounds found in the urine which bind H and serve

as another means of excreting H. These include phosphate, creatinine and other

urine constituents.


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Ammonium

Way of excreting H

Ammonium lost = bicarbonate returned

Remember that there is an overall excess of H in the body produced from the

processes discussed earlier. We talked about titratable acids earlier as one way

of excreting H. However, this method is not enough to handle the load from

production of nonvolatile acids. Ammonium serves another way of excreting H in

the urine.


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Net Acid Excretion NEA

Maximized when little bicarbonate lost

Bicarbonate freely filtered and almost entirely

reabsorbed

Rate of ammonium

excretion

Rate of titratable

acid excretionAmount of

bicarbonate lost in

urine

This is the equation for net acid excretion. Net acid excretion is equal to the rates of

excretion of ammonium and titratable acid minus the amount of bicarbonate lost in the

urine. From the equation, we can see that NAE is maximized when little or no

bicarbonoate is lost in the urine. This is actually normally the case because bicarbonate is

freely filtered is almost entirely reabsorbed.


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Bic

arbonate

Reab

sorption

This figure shows how much bicarbonate isreabsorbed by the different segments of the

nephron. The PT reabsorbs most of the

bicarbonate and the other segments are able

to reabsorb what is left of the filtered

bicarbonate. Almost no bicarbonate is lost in

the urine.


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oximal

ConvulutedTubule


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H is actively tranported out of the tubular cell via a NaHantiporter or a H ATPase. The NaK ATPase maintains the

intracellular concentration of Na low. This creates a gradient for

Na to be transported from the tubular fluid into the tubular cell.

As Na gets in, H goes out via the NaH antiporter. This is the

predominant pathwya for H secretion. The H ATPase directly uses

ATP to transport H out of the tubular cell.once in the tubular fluid,

H will combine with bicarbonate to form carbonic acid. CA

present in the brush border catalyzes the dehydration reaction to

yield CO2 and H2O which then diffuse back to the tubular cell.

Inside the cell, they again react via carbonic anhydrase which will

yield H and bicarbonate. H is secreted out via the mechanismsdiscussed earlier while bicarbonate is reabsorbed back to the

blood via either a Na3HCO3 symporter or a Cl-HCO3 antiporter.


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DT and CD

Two types of intercalated cells

Alpha secrete H/reabsorb bicarbonate

Beta secrete bicarbonate


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staltubu

leandcollecting

duct


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H is secreted from the alpha cell via two pathways: HK antiporter and an

HATPase. Movement of K into the cell is coupled with the movement of

H out of the cell. For the other protein, ATP is used to pump H out of the

cell. The secreted H combines with bicarbonate to form carbonic acid

which then dissociates to CO2 and H2O. These then diffuse back to the

cell. Carbonic anhydrase form bicarbonate and H. H is secreted again via

the two mechanisms described above while bicarbonate is reabsorbed

back to the blood via a Cl-HCO3 antiporter.


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staltubu

leandcollecting

duct


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The beta cells, instead of reabsorbing bicarbonate,

secrete bicarbonate. The key difference in this cell

compared to the alpha or H secreting/ bicarbonate

reabsorbing cell is the location of the H ATPase and the

Cl HCO3 antiporter. The Cl-HCO3 antiporter is located at

the apical side while the H ATPase is located in the

basolateral side.


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Most acidic of them all

PT has higher permeability to H and HCO3

than DT and CD.

Which segment is the most acidic of them all?

The segments of the nephron have different permeabilities to H and

bicarbonate. The proximal tubule is the most permeable to H and bicarbonate,thus it is able to reabsorb more H and bicarbonate. The urine in this segment

will then be less acidic pH 6.5 because H is reabsorbed. The DT and CD are not

very permeable to H. Thus the urine at this segment will be very acidic, ph 4.0,

because H is not reabsorbed and persists in the urine.


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Regulation of H Secretion

Acidosis stimulate H secretion

Alkalosis reduce H secretion

Acidosis or an excess of H will promote

secretion of H while alkalosis will reduce the

secretion of H. O di ba etong part na to madalilang intindihin. Gets agad.


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Metabolic Acidosis

Immediate decrease in intracellular pH

Cell-to-tubular fluid H gradient

Allosteric changes in transport proteins

More transporters shuttled to the membrane

Long term

Increased synthesis of transport proteins

Hormones Endothelin

Cortisol


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Depending on how long metabolic acidosis has been occuring, there

may be immediate and long term changes occurring in the cells of

the nephron. Metabolic acidosis causes the pH inside the tubularcell to decrease. This will create a more favorable cell-to-tubular

fluid gradient for H secretion. The increase in acidity also causes

allosteric changes in the transport proteins in these cells, which

result to enhancing their ability to secrete more H. Another

immediate result of a decrease in pH is the transport of moretransport proteins into the membranes of these cells. More

transport proteins means more H can be secreted out of the cell.

When metabolic acidosis becomes prolonged, the tubual cells

synthesize more transport proteins for H secretion.

Hormones also mediate these changes in H transport proteins.

These are endothelin and cortisol.


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Endothelin

Produced from endothelial and proximal

tubule cells

Stimulated by acidosis

Insertion of NaH and Na-3HCO3 into the apical

and basolateral membranes

Endothelin is produced from the endothelial cells and in the proximal tubulecells. Secretion of this hormone is stimulated by acidosis. This hormones

promotes insertion of transport proteins in the tubular cells which facilitate

secretion of H


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Cortisol

Produced from adrenal cortex

Stimulated by acidosis

Increases transcription and translation of NaHantiporter and Na-3HCO3 symporter genes

Secretion of coritsol is also stimulated by acidosis from the adrenal cortex.

This homone increases the transcription and translation of genes coding for

transport proteins which will facilitate H secretion


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Alkalosis

Increase in intracellular pH

Inhibits H secretion

Mechanisms reversed for acidosis

In alkalosis, the changes we have discussed are reversed. Alkalosis will

increase intracellular pH. A decrease in the H concentration inside the

tubular cells will inhibit secretion of H because of a less favorable gradientfor H transport out of the cell.


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Na affects H and HCO3

Na affects H secretion

NaH antiporter

Glomerulotubular balance GFR and PCT reabsorption GFR - filtered Na and HCO3 - more bicarbonate

reabsorbed

In the proximal tubule and the loop of Henle, the NaH antiporter is involved in H

secretion. Since this is an antiporter, change in Na will also affect H secretion. This will

also translate to a change in bicarbonate reabsorption since H secretion is also linked to

bicarbonate reabsorption.

Glomerulotubular balance matches the reabsorption at the PCT with the GFR. Thus

when the GFR increases, there will be more fluid reaching the PCT, and thus it will also

reabsorb more fluid, containing Na and HCO3.


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Volume Contraction

Negative Na balance

H secretion is enhanced via activation of RAAS

Peritubular capillary hydrostatic pressure

H secretion is also enhanced when there is volume contraction, or a Na deficit.

This condition activates the RAAS, whose overall effect is to retain water by

reabsorbing more Na. In our previous lecture, we talked about the changesoccuring in volume contraction. There is a decrease in peritubular capillary

hydrostatic pressure, which enhances Na and water reabsorption.


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Volume Contraction

Angiotensin II PCT Stimulate NaH antiporter and Na-HCO3 symporter

Insertion of more transporters

Aldosterone DT and CD

Hyperpolarizes transepithelial voltage Stimulate Na reabsorption in principal cells

Stimulate H secretion by intercalated cells

Angiotensin II acts on the PCT. It stimulates the NaH antiporter and Na-HCO3

symporter. Increasing the activity of these proteins will reabsorb more Na and

secrete more H. It also inserts more of these transport proteins in the cells of the PT.

Aldosterone on the other hand acts on the DT and CD. When it stimulates Na

reabsorption in the principal cells, the lumen becomes more electro negative or it

hyperpolarizes the transepithelial voltage. This will then facilitate the secretion of

positively charged H into the lumen.


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roximalConvu

lutedTubule


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H is actively tranported out of the tubular cell via a NaH antiporter

or a H ATPase. The NaK ATPase maintains the intracellular

concentration of Na low. This creates a gradient for Na to be

transported from the tubular fluid into the tubular cell. As Na gets

in, H goes out via the NaH antiporter. This is the predominant

pathwya for H secretion. The H ATPase directly uses ATP to

transport H out of the tubular cell.once in the tubular fluid, H willcombine with bicarbonate to form carbonic acid. CA present in the

brush border catalyzes the dehydration reaction to yield CO2 and

H2O which then diffuse back to the tubular cell. Inside the cell, they

again react via carbonic anhydrase which will yield H and

bicarbonate. H is secreted out via the mechanisms discussed earlierwhile bicarbonate is reabsorbed back to the blood via either a

Na3HCO3 symporter or a Cl-HCO3 antiporter.


36/83Latedistaltu

bulea

nd

collectingduct

Cl Cl

H2O

H2O


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The late distal tubule is composed of two cells, the principal cell and the intercalated

cell. Lets first discuss what the principal cell does. The reabsorption of Na, and

secretion of K depends on the activity of the NaK ATPase. Again, it maintains a low

intracellular sodium, creating a gradient which allows Na to be reabsorbed passively

through Epithelial Na-selective channels or ENaC in the apical membrane. Sodiumthen enters the blood via the action of the NaKATPase. The reabsorption of sodium,

creates a relative negative charge on the tubular fluid, since positively charged

sodium ions are removed from it. This will then form a gradient for Chloride to be

passively reabsorbed through the gap junctions via the paracellular pathway. Aside

from sodium, and chloride, water is also reabsorbed in the principal cells via

aquaporin channels located both in the apical and basolateral membranes of thetubular cells. We have now discussed how sodium, chloride and water are

reabsorbed by the principal cells.

Now we move on to how potassium is secreted in the principal cell. Potassium uptake

from the blood is done by the NaKATPase. This increases the K inside the principal

cells. K then moves out of the cell via diffusion, down its concentration gradient viaapical cell membrane K channels.

In the intercalated cell, K is reabsorbed via a K-H ATPase. It secretes either

bicarbonate or H, thus it is important in regulating acid-base balance. This will be

further discussed in the succeeding lectures.


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Volume Expansion

Positive Na balance

H secretion is reduced

Low angiotensin and aldosterone

Peritubular capillary hydrostatic pressure

During volume expansion, or positive Na balance, H secretion is reduced. Less Na is

reabsorbed from the tubules thus less H will be secreted via the NaH antiporter. TheRAAS will not be activated thus there will be low angiotensin and aldosterone which

promote Na reabsorption and H secretion in the tubules. An increase in peritubular

capillary hydrostatic pressure will inhibit Na reabsorption during volume expansion.

Inhibition of Na reabsorption will also inhibit secretion of H.


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PTH

Acute inhibits H secretion

Inhibits NaH antiport

Endocytosis

Chronic stimulates H secretion

TAL, DT

Renal response to acidosis

PTH has both as stimulatory and an inhibitory role in secretion of H. During acute

acidosis, PTH will inhibit secretion of H by inhibiting the action of the NaH antiporter

and promoting endocytosis of transport proteins in the apical membranes.

During chronic acidosis, PTH will stimulate the kidney to secrete H. This constitutes the

renal response to acidosis which is to secrete H.


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K

Hypokalemia acidifies tubular cells promotes H

secretion; increased HKATPase expression in

intercalated cells

Hyperkalemia alkalinizes tubular cells - inhibts Hsecretion

K-induced cellular changes

Changes in K also alter H secretion. K-induced cellular changes are thought to

influence the secretion of H from the tubular cells. Hypokalemia acidifies the cells

of the tubules, which promote H secretion. Aside from this mechanism,

hypokalemia also increases the experssion of HKATPase at the intercalated cells.

Hyperkalemia, on the other hand, alkalinizes the tubular cells, which inhibits H

secretion.


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Formation of New Bicarbonate

Reabsorption of HCO3 not enough

Formation of HCO3 needed

Excretion of titratable acid

Excretion of NH4

To maintain acid-base balance, the kidneys reabsorb bicarbonate. However, this is

not enough to replenish the bicarbonate lost from neutralizing the nonvolatile

acids. The kidneys must form new bicarbonate to replenish the bicarbonate lost,

and also to maintain acid-base balance. Generation of new bicarbonate is done by

excreting titratable acid and excretion of ammonium.


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Titratable Acid

HCO3 reabsorbed in PT and loop of Henle

Little HCO3 reach DT and CD

Secreted H combines with nonHCO3 buffers (P)

Insufficient to generate required amount of HCO3

The proximal tubule and the loop of Henle reabsorb bicarbonate. Thus the tubular

fluid reaching the DT and CD have very little amounts of bicarbonate available toneutralize the secreted H. Instead of combining with bicarbonate, H will combine

with non-HCO3 compounds, or urinary buffers such as phosphate. Since the secreted

H is formed inside the cell, formation of H also forms bicarbonate which is

reabsorbed back into the blood. Formation of titatable acid is not sufficient to

generate the appropriate amount of bicarbonate. This is augmented by the

formation and excretion of ammonium.


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This slide shows how the formation of a titratable acid is

able to generate bicarbonate, which is needed to

neutralize the formation of nonvolatile acids. Since the

tubular fluid reaching the DT and CD have low amount of

bicarbonate, the secreted H will combine with urinary

buffers such as phosphate. The combined H-buffer is then

excreted into the urine. The generation of H, which

occurred inside the cell, also generates bicarbonate via the

action of CA. This bicarbonate is reabsorbed back into theblood.


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Ammonium

Synthesis and excretion result to addition ofbicarbonate to ECF

Produced from glutamine ammoniagenesis

Secreted from PCT, reabsorbed in TAL,secreted in the CD

1 ammonium excreted = 1 bicarbonate

returnedThe synthesis and excretion of ammonium result to addition of bicarbonate to the ECF.

Ammonium comes from the breakdown of glutamine, a process called ammoniagenesis.

Ammonium is synthesized and secreted from the PCT. It is then reabsorbed in the TAL,

secreted again in the CD before getting excreted into the urine. Excretion of 1 molecule

of ammonium will result to a return of 1 molecule of bicarbonate to the ECF.


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This slide shows the complicated synthesis and excretion of

ammonium, and how this process is able to generate

bicarbonate. First lets look at the cell of the PCT. This is

where ammoniagenesis occurs. Glutamine is degraded into

ammonium and an anion (2-oxoglutarate). Metabolism of

this anion will yield 2 molecules of bicarbonate which will bereabsorbed back into the peritubular capillary. At this point,

we already have returned molecules of bicarbonate back to

the ECF. Now, lets talk about how ammonium is excreted

and why it is important.


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Excretion of Ammonium

Complex

If not excreted, NH4+ urea

Generates H

Consumes bicarbonate

The excretion of ammonium involves a complex process, as we will discuss later.

The formation of bicarbonate and ammonium from glutamine is not enough.

Ammonium still has to be excreted, because if not, it will be reabsorbed. When it

is reabsorbed, it will be converted to urea by the liver. This process will yield an

additional H, which will then be needed to be neutralized by consuming another

bicarbonate. Thus if ammonium is not excreted or is reabsorbed, we will not be

able to generate bicarbonate but instead will consume another bicarbonate.


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Ammonium

secreted from thePT


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Now lets discuss how ammonium is excreted. We have

formed ammonium from the metabolism of glutamine.

Ammonium can be secreted from the PT by a NaH

antiporter, with ammonium substituting for H. It may also

be deprotonated to ammonia, which can then diffuse outof the PT. Once in the tubular fluid, ammonia is then

protonated again because of the secreted H from the PT.

We have now secreted ammonium from the PT.


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Majority of the ammonium secreted from the PT gets reabsorbed in theTAL. The reabsorption of ammonium at this segment is mediated by the


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Ammonium

reabsorbed in the TAL-Na-K-2Cl symporter

-Positive transepithelial luminal

voltage

p g y

NaK2Cl symporter and a positive transepithelial luminal voltage. From

the TAL, the ammonium moves to the medullary interstitium.


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Secretion of Ammonium from CD

From interstitium to CD

First mechanism

Nonionic diffusion NH3 diffuses into CD

Diffusion trapping CD less permeable to NH4+

Second mechanism

NH4-H antiportersSecretion of ammonium moves ammonium

from the interstitium back into the lumen of

the CD. Secretion of ammonium involves two

mechanisms: noniondic diffusion and diffusion

trapping and via NH4-H antiporters.


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Secretion of NH4+ in

the CD-nonionic diffusion

-diffusion trapping


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The first mechanism for the secretion of ammonium involves

two processes: nonionic diffusion and diffusion trapping.From the medullary interstitium, ammonium diffused into the

CD as ammonia. This is nonionic diffusion. Once in the tubular

fluid, ammonia will be protonated by H secreted from the

intercalated cell of the CD. This will then form ammoniumagain. The CD is les permeable to ammonium than ammonia

because ammonium has a charge. Once inside the lumen of

the CD, ammonium will not be reabsorbed back into the

interstitium. This is diffusion trapping. Once trapped in the

tubular lumen, ammonium is excreted out into the urine.


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Secretion of NH4+ in

the CDNH4-H antiportersThe second mechanism for the secretion of ammonium in

the CD involves this antiporter. This antiporter secretes

ammonium out of the cell and transfer H back into the

cell. The secreted ammonium is then excreted in the

urine.


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Response to Acid base Disorders pH 7.35 to 7.45

Extracellular and intracellular buffering

Respiratory compensation Adjustments in renal net acid secretion

Minimize change in pHThe bodys pH is maintained at a very narrow range, at pH 7.35 to 7.45. The body pH

changes when there is any alteration in either the pCO2 or the bicarbonate. When there

is a change in the bodys pH, the body employs several mechanisms to defend against

the changes in pH. These mechanisms do not correct the pH but just minimizes the

change in pH imposed the a certain condition.


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Buffers

First line of defense

Extracellular instantaneous

Intracellular slower, minutes

Intracellular and extracellular buffers are the first line of defense against any changes

in pH. Effects of extracellular buffers are instanteneous while intracellular buffers are

slower, buffering pH in minutes.

Buffer Mechanism


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Buffer Mechanism

Extracellular

Acid added neutralized by HCO3 HCO3 consumed Alkali added neutralized by H more HCO3 produced

from H2CO3

Intracellular

acid added H moves into the cell

alkali added H moves out of the cellIn extracellular buffers, when acid is produced or added into the body, this acid is

neutralized by bicarbonate in the ECF. This consumes the bicarbonate thus lessening

the bicarbonate concentration in the ECF. When alkali is added, it will be neutralized by

H, which is produced from carbonic acid. This process will consume H, but will alsoproduce more bicarbonate as well.

In intracellular buffering, when acid is added, this will promote movement of H into the

cells. The H inside the cell will then be buffered by bicarbonate, phosphate, or proteins

inside the cell. When alkali is added, this will promote H to move out of the cell so it

can buffer the H outside.


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Bida ang Bicarbonate

Bicarbonate buffer system principal buffer of

ECF

Phosphate and plasma proteins provide

additional ECF buffering

The principal buffer in the ECF is the

bicarbonate buffer system. Phosphate and

plasma proteins provide additional buffering

capacity. B- bicarbonate = Bida


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HCO3 in Respiratory acid-base

PCO2

CO2 moves

inside cell

bicarbonategoes out

ECF

bicarbonate

PCO2

CO2

inside cell

bicarbonategoes out

ECF

bicarbonate


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This is how bicarbonate buffers the ECF during respiratory

acid-base disturbances. When there is an increase in PCO2 or

respiratory acidosis, more CO2 will move inside of the cell.This will shift the reaction towards the formation of more H

and HCO3. The formed H is buffered intracellularly while the

bicarbonate goes out of the cell. This will then increase the

ECF bicarbonate and thus decrease the change in pH inducedby the increase in pCO2.

On the other hand, if the pCO decreases, less CO2 will be

inside the cell. This will shift the reaction towards the

dissociation of carbonic acid to CO2 and H2O. Thus, there willbe less bicarbonate which will go out of the cell. And the ECF

bicarbonate will decrease.


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Respiratory Compensation

2nd line of defense

Response occurs in hours

Chemoreceptors in brainstem, carotid, aorticbodies sense changes in pCO2 and H

H - pH - RR

H - pH - RR


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Based on the HH equation, any change in pCO2 will alter

the bodys pH. Chemoreceptors found in the brainstem,carotid and aortic bodies sense changes in pCO2 and H.

These will then determine the ventilatory rate. When

there is metabolic acidosis, or an increase in H, the

respiratory rate is increased so that more CO2 will beblown off and the pCO2 will decrease. This will then

decrease the H. If there is metabolic alklaosis, or a

decrease in H, the respiratory rate will be decreased so

that more CO2 will be retained. This will then increase

the H. Adjustments in ventilatory may be initiated

immediately but full compensation might require several

hours to complete.


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Renal Adjustment

3rd line of defense

Response takes several days to complete

Renal adjustment to acid base disorders is the

3rd line of defense. It takes several days for the

kidneys to adjust so that the pH is maintained

at normal values.


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Renal Adjustment

Acidosis

H secretion entire filtered HCO3 reabsorbed

excretion oftitratable acid, production and

excretion of NH4, bicarbonate production

ECF bicarbonate

When there is acidosis, the tubules will secrete more H. The entire filtered load of

bicarbonate is also reabsorbed. Since there is excess of H, excretion of titratableacid and NH4 will increase as well. When these compounds are formed,

bicarbonate is also formed and is reabsorbed into the blood. This will then

increase the ECF bicarbonate and restore the pH back to normal.


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Renal Adjustment

Alkalosis

filtered load of HCO3, H secretion

HCO3 excretion, titratable acid and NH4

excretion

HCO3 in urine, net acid excretion

ECF bicarbonate

When there is alkalosis, there will be an increase in the filtered load of bicarbonatesince there is an excess of bicarbonate in the blood. Secretion of H in the collecting

duct will be inhibited. Bicarbonate excretion will increase and thus bicarbonate will

be found in the urine. A decrease in H secretion will also decrease synthesis and

excretion of titratable acid and ammonium resulting a decrease in net acid

excretion. All these processes will decrease ECF bicarbonate to restore pH back to

normal.


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Acid Base Disorders

Compensation only reduces the change in pH,

but does not correct the underlying cause of

the acid base disorder


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Acid base disorders include the following 4 disorders. When you have acidosis,

there is a decrease in pH. If you have alkalosis, you have an increase in your pH. In

metabolic acidosis, the primary problem is a deficiency in bicarbonate in the ECF. To

compensate for this, the 3 defense mechanisms we discussed earlier are used.

There is hyperventilation to decrease the pCO2 and increase in renal net acidexcretion to balance out the increase in pH. In metabolic alkalosis, the primary

problem is an excess of bicarbonate. Again, same mechanisms are involved to

decrease the change in pH. There will be hyperventilation and a decrease in net

acid excretion to compensate for the increase in pH.

In respiratory acid base balance, only two mechansims are involved for

compensation, since the respiratory system is already the problem. In respiratory

acidosis, there is an increase in pCO2. this is buffered by the ICF and the kidneys by

increasing net acid excretion. In respiratory alkalosis, there is a decrease in pCO2.

this is buffered by the ICF and the kidneys by decreasing net acid excretion.

The compensations we discussed only reduce the change in pH, to try to maintain

the pH at values which will still allow for life to continue without any problems.. The

compensation does not correct the underlying cause of the acid base disorder. Once

these mechanisms are overwhelmed, the acid base disorder will still persist unless

the underlying cause has been resolved.


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Metabolic Acidosis Causes

Addition of acid - diabetic ketoacidosis

Loss of base diarrhea

Failure to excrete H renal failure

Compensation

Buffering in ICF and ECF

pH stimulates respiratory center - RR - PCO2

NEA

The causes of metabolic acidosis include addition of acid such as in diabeticketoacidosis, loss of base as in diarrhea and failure to excrete H when you have

renal failure. The primary problem here is a deficiency in bicarbonate, and the

compensation for the change in pH is mediated by the buffers, decreasing the

pCO2 by increasing the RR, and increasing secretion of H by the kidneys.


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Metabolic Alkalosis Causes

Addition of base ingestion of antacids

Volume contraction hemorrhage

Loss of acid vomiting

Compensation

Decreased HCO3 reabsorption

pH inhibits respiratory center - RR - PCO2

Metabolic alkalosis is caused by addition of base such as in ingestion of antacids,volume contraction such as in hemorrhage and loss of acid during vomiting. The

primary problem here is an excess of bicarbonate. To offset this, this is buffered by

the ICF and ECF, the respiratory rate is decreased to increase the pCO2 and the

kidneys decrease the secretion of H.


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Respiratory Acidosis Decreased gas exchange

Inadequate ventilation (drug induced depression ofrespiratory center)

Impaired gas diffusion (pulmonary edema)

Compensation Acute ICF buffering

Chronic renal - Stimulate HCO3 reabsorption and

excretion of titratable acid, NH4 - NEA

Respiratory acidosis is primarily caused by a decrease in gas exchange. This is usually

caused by inadequate ventilation, probably from depression of the respiratory center, or

impairment in gas diffusion such as in pulmonary edema. The compensation in

respiratory acidosis is done by the kidneys by reabsorbing more HCO3 and excretion of

more titratable acid and NH4. however, this response will take several days so in the

acute setting, the buffering of the ICF maintain the pH at accetable levels.


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Respiratory Alkalosis Increased gas exchange

Increased ventilation (stimulation of respiratory centers,hyperventilation)

Compensation

Acute ICF buffering

Chronic inhibit HCO3 reabsorption, reduce excretion of

titratable acid, NH4 - NEA

Respiratory alkalosis is caused by an increase in gas exchange. This may occur when

there is increase in ventilation, such as when the respiratory centers are stimulated or

by hyperventilation caused by fear, anxiety or pain. In the acute phase, the ICF does the

buffering while in the chronic phase, the reabsorption of HCO3 is inhibited, and the

excretion of titratable acid and NH4 are also reduced. These events will lead to a

decrease in net acid excretion to compensate for the alkalosis.


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Analysis of Acid-Base Disorders

pH 7.35 (7.35-7.45)

HCO3 = 16 (24)

PCO2 = 30 (40)

Interpret this ABG result.


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Answer

1. acidosis

2. metabolic

3. compensated


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Key Concepts

The kidneys maintain acid-base balance throughthe excretion of an amount of acid equal to theamount of nonvolatile acid produced bymetabolism and the quantity ingested in the diet.

The kidneys also prevent the loss of HCO3- in

urine by reabsorbing virtually all the HCO3-

filtered at the glomeruli.

Both reabsorption of the filtered HCO3

-

andexcretion of acid are accomplished via secretionof H+ by nephrons


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Key Concepts

.Acid is excreted by the kidneys in the form of

titratable acid (primarily as Pi) and NH4+.

Excretion of both titratable acid and NH4+

results in the generation of new HCO3-, whichreplenishes the ECF HCO3

- lost during the

neutralization of nonvolatile acids.

K C


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Key Concepts

The body uses three lines of defense to

minimize the impact of acid-base disorders on

body fluid pH: (1) ECF and ICF buffering, (2)

respiratory compensation, and (3) renalcompensation.

K C


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Key Concepts

Metabolic acid-base disorders are caused by primaryalterations in ECF [HCO3

-], which in turn result from theaddition of acid to or loss of alkali from the body.

In response to metabolic acidosis, pulmonaryventilation is increased, which decreases PCO

2, and

renal net acid excretion is increased.

An increase in ECF [HCO3-] causes alkalosis. This

decreases pulmonary ventilation, which elevates PCO2.

The pulmonary response to metabolic acid-base

disorders occurs in a matter of minutes. Renal net acidexcretion is also decreased. This response may takeseveral days.

K C


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Key Concepts

Respiratory acid-base disorders result fromprimary alterations in PCO2.

Elevation of PCO2 produces acidosis, and the

kidneys respond with an increase in net acidexcretion.

Conversely, a reduction in PCO2 produces

alkalosis, and renal net acid excretion is reduced. The kidneys respond to respiratory acid-base

disorders over a period of several hours to days.

role of kidneys in the regulation of acid-base balance

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